In studies reported in the 1960s and since, blood plasma from radiation-exposed individuals has been shown to induce chromosome damage when transferred into lymphocyte cultures of non-irradiated persons. This effect has been described to occur via clastogenic factors, whose nature is still mostly unknown. We have previously examined clastogenic factors from irradiated individuals by looking at plasma-induced DNA damage in reporter cells. Plasma was tested from ca. 30 locally exposed clinical patients receiving fractionated radiation treatment, as well as from three radiological accident victims exposed in 1994, albeit sampled 14 years post-accident. In the current work, proteome changes in the plasma from all subjects were examined with 2D gel electrophoresis-based proteomics techniques, in order to evaluate the level of protein expression with respect to the findings of a clastogenic factor effect. No differences were observed in protein expression due to local radiation exposure (pre- vs post-exposure). In contrast, plasma from the radiation accident victims showed alterations in the expression of 18 protein spots (in comparison with plasma from the control group). Among these, proteins such as haptoglobin, serotransferrin/transferrin, fibrinogen and ubiquitin-60S ribosomal protein L40 were observed, none of them likely to be clastogenic factors. In conclusion, the proteomics techniques applied were unable to identify changes in the proteome of the locally irradiated patients, whereas such differences were observed for the accident victims. However, association with the clastogenic effect or any specific clastogenic factor remains unresolved and thus further studies with more sensitive techniques are warranted.